title: Genomic mapping of 5-hydroxymethylcytosine in the human brain.
abstract: Methylation at the 5-position of cytosine is a well-studied epigenetic pathway. In addition to 5-methylcytosine (5mC), substantial amounts of 5-hydroxymethylcytosine (5hmC) also referred to as the sixth DNA base have been detected in certain tissues, most notably the brain. However, the genomic distribution of this cytosine modification is unknown. Here, we have used an immunoprecipitation technique (5hmC-IP) to examine the occurrence of 5hmC in DNA from human brain frontal lobe tissue. The distribution of 5hmC was compared to that of 5mC. We show that 5hmC is more selectively targeted to genes than is 5mC. 5hmC is particularly enriched at promoters and in intragenic regions (gene bodies) but is largely absent from non-gene regions. 5hmC peaks at transcription start sites did not correlate with gene expression levels for promoters with intermediate or high CpG content. However, the presence of 5hmC in gene bodies was more positively correlated with gene expression levels than was the presence of 5mC. Promoters of testis-specific genes showed strong 5mC peaks in brain DNA but were almost completely devoid of 5hmC. Our data provide an overview of the genomic distribution of 5hmC in human brain and will set the stage for further functional characterization of this novel DNA modification.
authors.affiliation: Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
authors.forename: Seung-Gi
authors.initials: SG
authors.lastname: Jin
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.forename: Arthur X
authors.initials: AX
authors.lastname: Li
authors.forename: Gerd P
authors.initials: GP
authors.lastname: Pfeifer
mesh_terms: D044503:5-Methylcytosine / Q000032:analysis / Q000031:analogs & derivatives; D000818:Animals; D001923:Brain Chemistry; D003596:Cytosine / Q000031:analogs & derivatives* / Q000032:analysis; D004247:DNA / Q000737:chemistry*; D015870:Gene Expression; D023281:Genomics; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA